Immunoglobulin superfamily receptors: cis-interactions, intracellular adapters and alternative splicing regulate adhesion

The immunoglobulin domain is a module found in vertebrates and invertebrate s. Its ability to form linear rods when deployed in series, combined with i ts propensity to bind specifically to other proteins has made it ideal for building cell surface receptors and cell adhesion molecules. These features have resulted in the incorporation of immunoglobulin domains into many hun dreds of cell surface molecules. Recently three major advances have been ma de in understanding immunoglobulin receptors. One is the recognition that t heir intracellular binding partners are likely to link to multiple cell sur face molecules, allowing cross-talk or oligomeric complex formation. A seco nd, but related phenomenon, is their participation in cis-interactions on t he extracellular surface that regulate signaling or adhesion. The third is the dramatic ability to form dozens to thousands of different isoforms via alternative splicing. Although antibodies may have been the first example o f immunoglobulin-domain-containing proteins using cis-interactions to form receptor like molecules, and the grandest instance of diversity production from limited genetic material, these are clearly old ideas in this superfam ily.